Accès ouvert

Population pharmacokinetics of child-friendly dispersible amoxicillin/clavulanate tablets in African children with severe community acquired pneumonia

Article scientifique 2026 Autre

Résumé

Background: Severe community-acquired pneumonia (CAP) remains a leading cause of mortality in children under five. The PediCAP trial evaluated oral step-down therapy using dispersible amoxicillin or amoxicillin/clavulanate tablets in African children hospitalised with severe CAP. Dispersible tablet formulations are preferred in children; however, pharmacokinetic data for oral amoxicillin/clavulanate in paediatric populations remain limited. We characterised the pharmacokinetics of 4:1, 7:1, and 14:1 dispersible amoxicillin/clavulanate tablets in children enrolled in the PediCAP trial and predicted target attainment under different dosing schemes. Methods: Children were randomised within 24 hours of starting intravenous antibiotics to oral step-down therapy with weight-banded dosing of twice-daily amoxicillin/clavulanate (4:1, 7:1, or 14:1). Plasma concentrations were quantified following intensive sampling and analysed using nonlinear mixed-effects modelling with allometric scaling and postmenstrual age-dependent clearance maturation. Pharmacodynamic indices included %fT>MIC for amoxicillin and %fT>Ct for clavulanate. Results: A total of 157 children (median [range] age, 12 [2-70] months; weight, 8.4 [4.0-22.0] kg) contributed 707 paired concentrations. Amoxicillin was described by a two-compartment model and clavulanate by a one-compartment model, both with sequential zero- and first-order absorption. Typical clearance for an 8-kg individual at full maturation was 11.8L/h for amoxicillin and 6.1L/h for clavulanate. Pharmacokinetics were similar between the formulation ratios. Weight-banded dosing achieved balanced exposures across weight groups. Amoxicillin achieved 40%fT>MIC for MICs≤2mg/L. A proposed clavulanate target of 20%fT>0.5mg/L was achieved in most children even at the lowest amoxicillin/clavulanate ratio. Conclusion: Weight-banded dosing using dispersible amoxicillin/clavulanate tablets provide consistent exposure profiles in African children with severe CAP.

Citer ce document

Dyk, J., Gebreyesus, M., Clements, M., Standing, J., Moore, D., Dangor, Z., Waggie, Z., Spittle, B., Mulenga, V., Chabala, C., Mujuru, H., Buck, W., Sidat, M., Sacarlal, J., Bielicki, J., Musiime, V., Xu, H., Madhi, S., Sharland, M., Denti, P., Wasmann, R., PediCAP, M. (2026). Population pharmacokinetics of child-friendly dispersible amoxicillin/clavulanate tablets in African children with severe community acquired pneumonia. https://doi.org/10.64898/2026.09.18.26362138

Accès au document

Texte intégral en lecture en ligne, réservé aux abonnés SPHAERO et aux membres de l'institution. Se connecter

Voir l'article sur le site de la revue

Auteur(s)

Jennie van Dyk Manna Semere Gebreyesus Michelle Clements Joseph F. Standing David Paul Moore Ziyaad Dangor Zainab Waggie Ben Spittle Veronica Mulenga Chishala Chabala Hilda Mujuru W Chris Buck Muhammad Sidat Jahit Sacarlal Julia A. Bielicki Victor Musiime Hua Xu Shabir A. Madhi Mike Sharland Paolo Denti Roeland E. Wasmann MRCCTU PediCAP

Statistiques

Consultations : 1

Téléchargements : 0